Current public health guidelines recommend moderate-intensity aerobic (endurance) physical activity for a minimum of 30 min on five days each week or vigorous-intensity aerobic physical activity for a minimum of 20 min on three days each week. The guidelines specifically acknowledge that the point of maximum benefit for most health benefits has not been established. Our initial 7.8-year follow-up of the National Runners'Health showed that exceeding the current guideline levels was associated with significantly lower risks of cataracts (35%), macular degeneration (54%), hypertension (30%), hypercholesterolemia (47%), diabetes (68%), gout (45%), gallbladder disease (52%), diverticular disease (48%), benign prostate hyperplasia (33%), and nonfatal stroke (60%). To further demonstrate the potential benefits of exceeding guideline activity levels, we propose to compare moderate-intensity (walking) and vigorous intensity physical activity (running) to total and cause- specific mortality in 45,685 participants of the National Walkers'Health Study and 59,165 participants of the second National Runners'Health Study who surveyed at baseline between 1998-2000, and 54,960 participants of the original National Runners'Health Study were surveyed at baseline between 1991 and 1993. We estimate that 26,172 deaths will have occurred during the two million person years of follow-up, including 863 fatal colon, 426 breast, and 501 prostate, and 8,030 total cancers, 5,714 ischemic heart disease deaths, and 2,259 fatal myocardial infarctions. Three-year support is requested to obtain and analyze the National Death Index retrieval of cause of death in order to: 1: Define separately within the walkers'(N=45,685) and the combined runners'cohort (N=114,719) the dose- response relationships of total and cause-specific mortality vs. the amount, duration, intensity, and frequency of physical activity. 2: Test whether equivalent doses (i.e., MET-hours) of moderate-intensity (walking, N=45,685) and vigorous- intensity activity (running, N=59,165) yield comparable reductions in total and cause-specific mortality. 3: Test within the combined runners'cohorts whether cardiorespiratory fitness significantly predicts total and cause-specific mortality independent of physical activity (N=84,120, representing 72% of the sample reporting 10-km performance times). 4: Test within the original runners'cohort (N=54,960) whether change in activity during the 7.8 years between the first and second survey affects total and cause-specific mortality during the subsequent 11-year follow-up. 5: Test separately within the walkers (N=45,685) and combined runners'cohorts (N=114,125) whether or longest usual walk or run (including marathon training) significantly predicts total and cause-specific mortality independent of usual physical activity. 6: Test whether body weight or size mediates the relationships and differences of aims 1-5. PUBLIC HEALTH RELEVANCE: Narrative This application requests salary support for the principal investigator to apply his 20 years of biostatistical experience to analyze a large cohort of walkers and runners to determine the health benefits of vigorous exercise, marathon participation, and interactions with other variables on cardiovascular disease, diabetes, hypertension, gout, gallbladder disease, benign prostatic hyperplasia and other health endpoints. This application is concerned exclusively with the interpretation of actual data and not the collection of new data. The major objective is to better define the dose and intensity of physical activity for optimal health.